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Identification of genes key to leukaemia development offers hope of effective treatment

Published
Tuesday 12 January 2016 Published Tue 12 Jan 2016

Adapted Media Release

Two genes have been identified that are critical to the development of the biggest leukaemia killer, acute myeloid leukaemia (AML). Researchers at King's College London found that drugs that selectively block these genes could be highly effective in treating this type of leukaemia.

The genes 'KDM4C' and 'PRMT1' ordinarily play a role in translating the genetic information in DNA into healthy cell functions. The researchers have shown, however, that during leukaemia development these enzymes are recruited to enable the transformation of blood cells into cancer cells. Crucially, these genes work in tandem and if either is not fully active, leukaemia is not able to develop.

In a report published in the journal Cancer Cell, the scientists used genetic tools to silence the two genes, as well as drugs to block their activity, in mice with AML. When either gene was silenced, the majority of the mice were still alive at the end of the 60-day experiment, whereas without treatment, the majority died in under 40 days. By blocking either gene's activity with drugs, which is more relevant to how human patients would be treated, the survival times for mice with AML were also significantly extended.

Blocking PRMT1 meant half the mice were still alive after 48 days, compared to 36 days for mice who did not receive treatment. Strikingly, leukaemia development was even more effectively suppressed in mice with AML by using a drug to block KDM4C activity instead. All of the mice treated with a KDM4C blocker were still alive at the end of the experiments while the group without treatment succumbed to the disease.

The research was funded by the blood cancer charity Bloodwise with additional funding from Cancer Research UK.

Professor Eric So, who led the research at King's College London, said: "The demonstration of how critical these genes are to cancer transformation and treatment could be highly significant for the design of new drugs. Further work is needed to develop and refine drugs to maximise their effects and so that they are suitable for patients. Clinical trials will then be needed to see how leukaemia patients respond to these drugs and how use of them can be optimised."

AML is diagnosed in around 2,400 people each year in the UK. Treatment aimed at a cure still mainly consists of gruelling chemotherapy that is normally too toxic for patients over the age of 60. Currently only one in five patients will survive for more than five years after diagnosis.

Dr Matt Kaiser, Head of Research at Bloodwise, said: "Patients with acute myeloid leukaemia have not yet benefited from the new era of precision medicine that has taken place in many other types of leukaemia. While this research is at an early stage, the possibility of developing drugs that can specifically target the cancer cells, without the life-threatening side-effects of traditional chemotherapy, is very exciting."

Dr Aine McCarthy, science information officer at Cancer Research UK, said: "Identifying weaknesses in acute myeloid leukaemia cells is the key to developing much needed new treatments for the disease - and to helping more people survive. This exciting new research has found a new way to target this disease and we look forward to seeing how this could help patients in the future."

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